P1526: THE RISK OF DEVELOPING PNEUMOCYSTIS JIROVECII PNEUMONIA PERSISTS EVEN AFTER COMPLETION OF IMMUNOSUPPRESSANTS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION RECIPIENTS
Authors: Takahide Ara, Shota Yokoyama, Yuta Hasegawa, Hiroyuki Ohigashi, Toshihiro Matsukawa, Atushi Yasumoto, Souichi Shiratori, Hideki Goto, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background:Pneumocystis jirovecii pneumonia (PjP) is a life-threatening infection in allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients. Trimethoprim/sulfamethoxazole (TMP/SMX) is the preferred primary prophylaxis of PjP after allo-SCT. The recommended dose is either a single-strength (80/400mg) tablet daily or a double-strength (160/800mg) tablet three times weekly but has significant toxicity. Furthermore, although the guidelines recommend the duration of prophylaxis from engraftment until >6 months after transplantation or as long as immunosuppressant is ongoing, it is still unclear whether this strategy is appropriate. Aims: To examine the appropriate prophylactic strategy for PjP by reviewing the incidence of PjPs and the status of prophylactic regimens for PjP in allo-SCT recipients. Methods: We retrospectively analyzed consecutive 437 patients who underwent allo-SCT at Hokkaido University Hospital from January 2012 to March 2021. Possible, probable and proven PjPs were diagnosed according to the EORTC/MSG criteria. The patients receiving TMP/SMX were divided into two groups based on whether their doses were guideline-recommended doses (Standard dose [SD] of TMP/SMX) or less (Low dose [LD] of TMP/SMX). Results: Four hundred thirty-seven patients with a median age 50 years (range, 17 - 70) included 189 AML, 69 MDS, 82 ALL, 46 lymphoma, and 51 other hematological diseases. Of these patients, 77, 245, and 115 patients underwent bone marrow transplantation, peripheral blood stem cell transplantation, and cord blood transplantation, respectively. About half of patients (48.5%) received reduced intensity conditioning (RIC) regimens. A total of 20 patients (probable; n=19, possible; n=1) developed PjPs (5.48%) at a median of 238 days (range, 13 - 867 days) after allo-SCT (Figure A). Although 5 of 20 patients who developed PjPs had a history of prophylaxis for PjP, all of them were not taking the prophylactic drugs at the onset (Figure B). Moreover, 10 of 20 patients developed PjPs with a median of 102.5 days (range, 21 - 469 days) after completion of immunosuppressants. In multivariate analysis, no history of prophylaxis (HR 4.117, [95% CI, 1.526 - 11.110]; P=0.0052) and receiving RIC regimens (HR 3.084, [95% CI, 1.115 - 8.529]; P=0.0300) were independent risk factors for developing PjPs. From these findings, it is important to continue the prophylaxis for a long term without adverse events in PjP. A total of 347 regimens (SD of TMP/SMX; n=185, LD of TMP/SMX; n=98, Atovaquone; n=48, Aerosolized Pentamidine; n=16) during a median follow up of 573 days (range, 10 - 3557 days) were administered in 233 patients in this period. Most patients receiving LD of TMP/SMX took a single-strength tablet twice or three times weekly. The median duration of prophylaxis of SD of TMP/SMX, LD of TMP/SMX, Atovaquone, and Aerosolized Pentamidine were 97 days (range, 2 - 2455 days), 124 days (range, 6 - 2415 days), 145.5 days (range, 0 - 1348 days), 94 days (range, 0 - 383 days), respectively. Importantly, the patients receiving LD of TMP/SMX had significantly fewer discontinuation due to adverse events than those receiving SD of TMP/SMX (P=0.00375, Figure C). Summary/Conclusion: The risk of developing PjP may be prolonged for a certain period even after completion of immunosuppressants. To prevent PjP, it is important to establish the prophylactic regimen which enables to continue long-term without toxicity. Low dose of TMP/SMX may be a promising option of the prophylaxis for PjP. Further prospective studies are warranted to confirm these findings.Keywords: Prevention, Allogeneic hematopoietic stem cell transplant, Infection